CD39, or vascular adenosine triphosphate diphosphohydrolase, has been considered an important inhibitor of platelet activation. Unexpectedly, cd39-deficient mice had prolonged bleeding times with minimally perturbed coagulation parameters. Platelet interactions with injured mesenteric vasculature were considerably reduced in vivo and purified mutant platelets failed to aggregate to standard agonists in vitro. This platelet hypofunction was reversible and associated with purinergic type P2Y1 receptor desensitization. In keeping with deficient vascular protective mechanisms, fibrin deposition was found at multiple organ sites in cd39-deficient mice and in transplanted cardiac grafts. Our data indicate a dual role for adenosine triphosphate diphosphohydrolase in modulating hemostasis and thrombotic reactions.
This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure.
Background: Portal vein embolization (PVE) has become a standard procedure to increase the future liver remnant (FLR) and enable curative resection of initially unresectable liver tumours. This study investigated the safety and feasibility of a new two-stage liver resection technique that uses in situ liver transection (ISLT) and portal vein ligation before completion hepatectomy.
Conclusion:ISLT is an effective and reliable technique to induce rapid growth of the FLR, even in patients with insufficient volume increase after PVE.
The liver has a large capacity for regeneration after resection. However, below a critical level of future liver remnant volume (FLRV), partial hepatectomy is accompanied by a significant increase of postoperative liver failure. There is accumulating evidence for the contribution of bone marrow stem cells (BMSCs) to participate in liver regeneration. Here we report on three patients subjected to intraportal administration of autologous CD133 + BMSCs subsequent to portal venous embolization of right liver segments, used to expand left lateral hepatic segments as FLRV. Computerized tomography scan volumetry revealed 2.5-fold increased mean proliferation rates of left lateral segments compared with a group of three consecutive patients treated without application of BMSCs. This early experience with portovenous application of CD133 + BMSCs could suggest that this novel therapeutic approach bears the potential of enhancing and accelerating hepatic regeneration in a clinical setting. Stem Cells 2005;23:463-470
In patients with malignant liver lesions, the combination of PVE with CD133(+) BMSC administration substantially increased hepatic regeneration compared with PVE alone.
These observations indicate a potentially important molecular barrier involving blood coagulation that may impact on the planned clinical application of porcine transgenic organs.
Ectonucleotidases influence purinergic receptor function by the hydrolysis of extracellular nucleotides. CD39 is an integral membrane protein that is a prototype member of the nucleoside 5-triphosphate diphosphohydrolase family. The native CD39 protein has two intracytoplasmic and two transmembrane domains. There is a large extracellular domain that undergoes extensive glycosylation and can be post-translationally modified by limited proteolysis. We have identified a potential thioester linkage site for S-acylation within the N-terminal region of CD39 and demonstrate that this region undergoes palmitoylation in a constitutive manner. The covalent lipid modification of this region of the protein appears to be important both in plasma membrane association and in targeting CD39 to caveolae. These specialized plasmalemmal domains are enriched in G protein-coupled receptors and appear to integrate cellular activation events. We suggest that palmitoylation could modulate the function of CD39 in regulating cellular signal transduction pathways.The vascular ATP or NTP diphosphohydrolase (ATPDase or NTPDase; EC 3.6.1.5), 1 now known to be CD39, is a plasma membrane-bound enzyme that plays the dominant role in the hydrolysis of extracellular tri-and/or diphosphate nucleotides in blood (1, 2). Our recent data from cd39-null mice indicate that this specific ectonucleotidase also plays a pivotal role in the regulation of an ADP-purinoreceptor P2Y1 function; absence of ATPDase activity results in desensitization of this G protein-coupled receptor with profound effects on hemostasis and thromboregulation (3).Established topological models of CD39 suggest the presence of two transmembrane domains at both termini of the molecule and an extracellular loop containing a central hydrophobic region (1,4,5). The transmembrane domains of ATPDases appear to influence the formation of detergent-sensitive multimers (6). Examination of CD39 amino acid sequences reveals a total of 11 cysteine (Cys) residues, with an unpaired Cys 13 contained within the intracellular N terminus of the protein (4). Analysis of the CD39 sequence, by a computer algorithm PROSITE, further indicates six putative N-glycosylation sites with several potential casein kinase, cAMP/cGMP-dependent protein kinase or protein kinase C phosphorylation sites (7, 8).We have described several post-translational modifications of CD39. There are differences in the extent of glycosylation of human CD39 in endothelial cells, platelets, and leukocytes (9). Effects of limited serine proteolysis of native CD39 on ATPDase activity have been documented (5), and there is also a propensity for CD39 to undergo autophosphorylation reactions (data not shown). In addition, we have shown that cellular interactions with free fatty acids modulate ATPDase enzymatic activity in vitro and have postulated that acylation could also influence CD39 structure (10). Here we study this possibility and specifically examine palmitoylation, a reversible and potentially regulated post-translational modificat...
Background: To evaluate the expression and test the clinical significance of the epithelial cellular adhesion molecule (Ep-CAM) in esophageal squamous cell carcinoma (SCC) to check the suitability of esophageal SCC patients for Ep-CAM directed targeted therapies.
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